Abstract
A novel approach was used to estimate the in vivo mutation rate of the retinoblastoma gene. A mathematical formula can be used to calculate the probability of neoplasia induced by one or more mutations in a population of dividing cells. This formula can then be applied to epidemiological data on hereditary and sporadic retinoblastoma. The analysis yields an estimate of the in vivo mutation rate of 8 x 10(-8)/gene/cell division (range 5.5 x 10(-8) to 1.3 x 10(-7]. The estimated non-replication association in vivo mutation rate is 2.4 x 10(-8)/gene/year (range 0 to 6.8 x 10(-8]. The formula is an improvement on previous attempts to produce a model of the process of mutation during cell generation. It can be applied to neoplastic disease in both children and adults.